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Sökning: WFRF:(Lundqvist Karin)

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1.
  • Austeng, Dordi, et al. (författare)
  • Incidence of and risk factors for neonatal morbidity after active perinatal care : extremely preterm infants study in Sweden (EXPRESS)
  • 2010
  • Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 99:7, s. 978-992
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: The aim of this study was to determine the incidence of neonatal morbidity in extremely preterm infants and to identify associated risk factors. Methods: Population based study of infants born before 27 gestational weeks and admitted for neonatal intensive care in Sweden during 2004-2007. Results: Of 638 admitted infants, 141 died. Among these, life support was withdrawn in 55 infants because of anticipation of poor long-term outcome. Of 497 surviving infants, 10% developed severe intraventricular haemorrhage (IVH), 5.7% cystic periventricular leucomalacia (cPVL), 41% septicaemia and 5.8% necrotizing enterocolitis (NEC); 61% had patent ductus arteriosus (PDA) and 34% developed retinopathy of prematurity (ROP) stage >= 3. Eighty-five per cent needed mechanical ventilation and 25% developed severe bronchopulmonary dysplasia (BPD). Forty-seven per cent survived to one year of age without any severe IVH, cPVL, severe ROP, severe BPD or NEC. Tocolysis increased and prolonged mechanical ventilation decreased the chances of survival without these morbidities. Maternal smoking and higher gestational duration were associated with lower risk of severe ROP, whereas PDA and poor growth increased this risk. Conclusion: Half of the infants surviving extremely preterm birth suffered from severe neonatal morbidities. Studies on how to reduce these morbidities and on the long-term health of survivors are warranted.
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  • Fellman, Vineta, et al. (författare)
  • One-year survival of extremely preterm infants after active perinatal care in Sweden.
  • 2009
  • Ingår i: JAMA : the journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 301:21, s. 2225-33
  • Tidskriftsartikel (refereegranskat)abstract
    • Up-to-date information on infant survival after extremely preterm birth is needed for assessing perinatal care services, clinical guidelines, and parental counseling.
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4.
  • Serenius, Fredrik, 1939-, et al. (författare)
  • Neurodevelopmental outcome in extremely preterm infants at 2.5 years after active perinatal care in Sweden.
  • 2013
  • Ingår i: Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 309:17, s. 1810-20
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance Active perinatal care increases survival of extremely preterm infants; however, improved survival might be associated with increased disability among survivors. Objective To determine neurodevelopmental outcome in extremely preterm children at 2.5 years (corrected age). Design, Setting, and Participants Population-based prospective cohort of consecutive extremely preterm infants born before 27 weeks of gestation in Sweden between 2004 and 2007. Of 707 live-born infants, 491 (69%) survived to 2.5 years. Survivors were assessed and compared with singleton control infants who were born at term and matched by sex, ethnicity, and municipality. Assessments ended in February 2010 and comparison estimates were adjusted for demographic differences. Main Outcomes and Measures Cognitive, language, and motor development was assessed with Bayley Scales of Infant and Toddler Development (3rd edition; Bayley-III), which are standardized to mean (SD) scores of 100 (15). Clinical examination and parental questionnaires were used for diagnosis of cerebral palsy and visual and hearing impairments. Assessments were made by week of gestational age. Results At a median age of 30.5 months (corrected), 456 of 491 (94%) extremely preterm children were evaluated (41 by chart review only). For controls, 701 had information on health status and 366 had Bayley-III assessments. Mean (SD) composite Bayley-III scores (cognition, 94 [12.3]; language, 98 [16.5]; motor, 94 [15.9]) were lower than the corresponding mean scores for controls (cognition, 104 [10.6]; P < .001; adjusted difference in mean scores, 9.2 [99% CI, 6.9-11.5]; language, 109 [12.3]; P < .001; adjusted difference in mean scores, 9.3 [99% Cl, 6.4-12.3]; and motor, 107 [13.7]; P < .001; adjusted difference in mean scores, 12.6 [99% Cl, 9.5-15.6]). Cognitive disability was moderate in 5% of the extremely preterm group vs 0.3% in controls (P < .001) and it was severe in 6.3% of the extremely preterm group vs 0.3% in controls (P < .001). Language disability was moderate in 9.4% of the extremely preterm group vs 2.5% in controls (P < .001) and severe in 6.6% of the extremely preterm group vs 0% in controls (P < .001). Other comparisons between the extremely preterm group vs controls were for cerebral palsy (7.0% vs 0.1%; P < .001), for blindness (0.9% vs 0%; P = .02), and for hearing impairment (moderate and severe, 0.9% vs 0%; P = .02, respectively). Overall, 42% (99% CI, 36%-48%) of extremely preterm children had no disability, 31% (99% CI, 25%-36%) had mild disability, 16% (99% CI, 12%-21%) had moderate disability, and 11% (99% CI, 7.2%-15%) had severe disability. Moderate or severe overall disability decreased with gestational age at birth (22 weeks, 60%; 23 weeks, 51%; 24 weeks, 34%; 25 weeks, 27%; and 26 weeks, 17%; P for trend < .001). Conclusions and Relevance Of children born extremely preterm and receiving active perinatal care, 73% had mild or no disability and neurodevelopmental outcome improved with each week of gestational age. These results are relevant for clinicians counseling families facing extremely preterm birth. JAMA. 2013;309(17):1810-1820
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5.
  • Serenius, Fredrik, et al. (författare)
  • Neurodevelopmental Outcome in Extremely Preterm Infants at 2.5 Years After Active Perinatal Care in Sweden
  • 2013
  • Ingår i: Obstetrical and Gynecological Survey. - : Lippincott Williams & Wilkins. - 0029-7828 .- 1533-9866. ; 68:12, s. 781-783
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    •  A proactive approach to the care of extremely preterm infants has increased survival and lowered the gestational age of viability, but these improvements may be associated with later neurodevelopmental disability. EXPRESS is a national population-based prospective study of all infants born alive or stillborn at less than 27 weeks’ gestation between 2004 and 2007 in Sweden. This prospective follow-up study was undertaken to assess neurologic and developmental outcome of the EXPRESS cohort at 2.5 years corrected age compared with a matched control group born at term.Of 707 live-born infants, 497 (70%) survived to corrected age 2.5 years; the final cohort included 491 children. Each preterm child was matched with 2 control subjects at 2.5 years chronological age. Cognitive, language, and motor development were assessed with the Bayley Scales of Infant and Toddler Development (Bayley III). Cerebral palsy (CP), visual and hearing disability, and a composite outcome of overall disabilities were assessed. The overall outcome was characterized as no, mild, moderate, and severe disability.Of 415 infants assessed with clinical examinations, 399, 393, and 382, respectively, completed the Bayley III cognitive, language, and motor scales; 366 control children were assessed with Bayley III. The mean composite cognitive, language, and motor scores for children in the preterm and control groups were 94 ± 12 and 104 ± 11, respectively (P < 0.001), 98 ± 17 and 109 ± 12 (P < 0.001), respectively, and 94 ± 16 and 107 ± 14 (P < 0.001), respectively. Normal cognitive development or mild cognitive disability was found in 354 preterm children (88.8%) and 364 control children (99.5%). Moderate or severe cognitive disability was present in 20 preterm children (5.0%) and 1 control child (0.3%) (P < 0.001) and in 25 (6.3%) and 1 (0.3%), respectively (P < 0.001). Normal language development or mild language disability was found in 330 children (83.9%) in the preterm group and with 351 (97.5%) in the control group (all group comparisons, P < 0.001). Normal motor development or mild motor disability occurred in 324 (84.8%) and 348 (98.6%) of children in the preterm and control groups, respectively. Moderate or severe mental developmental delay was seen in 88 and 10 children (20% and 2.8%), respectively (P < 0.001).In the preterm group, Bayley III cognitive, language, and motor scores increased with advancing gestational age at birth by 2.5 points (99% confidence interval [CI], 1.0–4.0) per week (P < 0.001), by 3.6 points (99% CI, 1.6–5.6) per week (P < 0.001), and by 2.5 points (99% CI, 0.5–4.5) per week scores (P = 0.001), respectively. Cerebral palsy was present in 32 preterm children (7.0%; 99% CI, 3.9–10.1%). Of 456 preterm children, 42.1% were classified as normal, 30.7% as having mild disabilities, and 27.2% as having moderate or severe disabilities (vs 78.1%, 18.6%, 3.3% of control subjects, respectively; P < 0.001 for all comparisons). The proportion of children with mild or no disabilities increased from 40% at 22 weeks to 83% at 26 weeks (P < 0.001 for trend). Moderate or severe disabilities decreased from 60% at 22 weeks to 17% at 26 weeks (P < 0.001 for trend).The impact of prematurity on neurodevelopmental outcome indicates that further improvements in neonatal care are necessary. Although preterm children had poorer neurodevelopmental outcomes than those born at term, 73% had no or mild disability, and neurodevelopmental outcome improved with each week of gestational age. These results are relevant for clinicians counseling couples facing extremely preterm birth of their infant
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6.
  • Stinesen-Kollberg, Karin, et al. (författare)
  • Reduced vaginal elasticity, reduced lubrication, and deep and superficial dyspareunia in irradiated gynecological cancer survivors
  • 2015
  • Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 54:5, s. 772-779
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose. The purpose of this study was to examine whether or not vaginal elasticity or lack of lubrication is associated with deep or superficial dyspareunia. We investigated gynecological cancer survivors treated with radiation therapy. Methods. In a population-based study with 616 women answering a questionnaire (participation rate 78%) and who were treated with radiotherapy for gynecological cancer, we analyzed information from 243 women (39%) who reported that they had had intercourse during the previous six months. Analyses included log-binomial regression (relative risks) and multiple imputations by chained equations in combination with Bayesian Model Averaging, yielding a posterior probability value. Age range of this cancer recurrent-free group of women was 29-80. Results. Dyspareunia affected 164 of 243 of the women (67%). One hundred thirty-four women (55%) reported superficial pain, 97 women (40%) reported deep pain, and 87 women (36%) reported both types of dyspareunia. The relative risk (RR) of deep dyspareunia was 1.87 (CI 1.41-2.49) with impaired vaginal elasticity compared to normal vaginal elasticity. Age and lower abdominal swelling were separate risk factors for deep dyspareunia. However, effects remain after adjusting for these factors. Conclusion. The relative risk of deep dyspareunia was almost twice as high with impaired vaginal elasticity compared to normal vaginal elasticity. If we wish to treat or even prevent deep dyspareunia in women with gynecological cancer, we may use our knowledge of the pathophysiology of deep dyspareunia and increasingly provide dilators together with instructions on how to use them for stretching exercises in order to retain vaginal elasticity. Results highlight the need for studies with more precise questions distinguishing superficial from deep dyspareunia so that in the future we may be able to primarily try to avoid reduced vaginal elasticity and secondarily reduce the symptoms.
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8.
  • Ahrens, Lutz, et al. (författare)
  • The relevant role of ion mobility separation in LC-HRMS based screening strategies for contaminants of emerging concern in the aquatic environment
  • 2021
  • Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 280
  • Tidskriftsartikel (refereegranskat)abstract
    • Ion mobility separation (IMS) coupled to high resolution mass spectrometry (IMS-HRMS) is a promising technique for (non-)target/suspect analysis of micropollutants in complex matrices. IMS separates ionized compounds based on their charge, shape and size facilitating the removal of co-eluting isomeric/isobaric species. Additionally, IMS data can be translated into collision cross-section (CCS) values, which can be used to increase the identification reliability. However, IMS-HRMS for the screening of contaminants of emerging concern (CECs) have been scarcely explored. In this study, the role of IMS-HRMS for the identification of CECs in complex matrices is highlighted, with emphasis on when and with which purpose is of use. The utilization of IMS can result in much cleaner mass spectra, which considerably facilitates data interpretation and the obtaining of reliable identifications. Furthermore, the robustness of IMS measurements across matrices permits the use of CCS as an additional relevant parameter during the identification step even when reference standards are not available. Moreover, an effect on the number of true and false identifications could be demonstrated by including IMS restrictions within the identification workflow. Data shown in this work is of special interest for environmental researchers dealing with the detection of CECs with state-of-the-art IMS-HRMS instruments.
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10.
  • Almstedt, Karin, 1980-, et al. (författare)
  • Unfolding a folding disease: folding, misfolding and aggregation of the marble brain syndrome-associated mutant H107Y of human carbonic anhydrase II
  • 2004
  • Ingår i: Journal of Molecular Biology. - Oxford : Elsevier. - 0022-2836 .- 1089-8638. ; 342:2, s. 619-633
  • Tidskriftsartikel (refereegranskat)abstract
    • Most loss-of-function diseases are caused by aberrant folding of important proteins. These proteins often misfold due to mutations. The disease marble brain syndrome (MBS), known also as carbonic anhydrase II deficiency syndrome (CADS), can manifest in carriers of point mutations in the human carbonic anhydrase II (HCA II) gene. One mutation associated with MBS entails the His107Tyr substitution. Here, we demonstrate that this mutation is a remarkably destabilizing folding mutation. The loss-of-function is clearly a folding defect, since the mutant shows 64% of CO2 hydration activity compared to that of the wild-type at low temperature where the mutant is folded. On the contrary, its stability towards thermal and guanidine hydrochloride (GuHCl) denaturation is highly compromised. Using activity assays, CD, fluorescence, NMR, cross-linking, aggregation measurements and molecular modeling, we have mapped the properties of this remarkable mutant. Loss of enzymatic activity had a midpoint temperature of denaturation (Tm) of 16 °C for the mutant compared to 55 °C for the wild-type protein. GuHCl-denaturation (at 4 °C) showed that the native state of the mutant was destabilized by 9.2 kcal/mol. The mutant unfolds through at least two equilibrium intermediates; one novel intermediate that we have termed the molten globule light state and, after further denaturation, the classical molten globule state is populated. Under physiological conditions (neutral pH; 37 °C), the His107Tyr mutant will populate the molten globule light state, likely due to novel interactions between Tyr107 and the surroundings of the critical residue Ser29 that destabilize the native conformation. This intermediate binds the hydrophobic dye 8-anilino-1-naphthalene sulfonic acid (ANS) but not as strong as the molten globule state, and near-UV CD reveals the presence of significant tertiary structure. Notably, this intermediate is not as prone to aggregation as the classical molten globule. As a proof of concept for an intervention strategy with small molecules, we showed that binding of the CA inhibitor acetazolamide increases the stability of the native state of the mutant by 2.9 kcal/mol in accordance with its strong affinity. Acetazolamide shifts the Tm to 34 °C that protects from misfolding and will enable a substantial fraction of the enzyme pool to survive physiological conditions.
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